Systemic delivery of trophic factors, such as Nerve Growth Factor (NGF), is difficult to accomplish inasmuch as the human body contains enzymes within the circulatory system which would rapidly degrade trophic factors. Biological investigations of delivery of trophic factors so far have been limited to injection of large amounts of NGF to laboratory animals in order to study the effects of NGF on treatment of nerve damage. Such injections typically require large amounts of NGF because of rapid degradation.
Delivery systems for introducing proteins and other compounds into animals are well known. Of increasing interest are lipid membrane vesicles, e.g., liposomes for use in drug delivery systems. For example, U.S. Pat. No. 4,522,803 and PCT Application No. U.S. Pat. No. 85/00220 describe liposome preparations in the form of multilamellar vesicles to entrap bioactive compounds, such as hormones, proteins, or glycoproteins, for delivery of the bioactive compound to a target tissue. A study of glycolipid-liposome formulations for delivery of enzymes to target organs showed that sugar residues of the glycolipid component can affect distribution of the enzyme within the target organ [M. Naoi et al, Biochemistry lnternational, 9, 267-272 (1984)]. Japanese Patent Document No. 57-146,710 describes liposome-type microcapsules having membrane walls composed of various components, such as phospholipids, gangliosides, cerebrosides and sulfatides, which encapsulate enzymes for delivery across the blood brain barrier.
Modified liposomes of various types have been devised and investigated as delivery vehicles in biological systems. For example, liposome formulations having different types of glycosides grafted onto liposome surfaces have been investigated for effect on tissue distribution of .sup.125 I-gamma-globulin [P. Ghosh et al, Biochimica et Biophysica Acta., 632(4), 562-572 (1980)]. Multilamellar liposomes have been prepared having a marker compound (ethylenediaminetetraacetic acid, EDTA) encapsulated within a shell wall membrane composed of various asialoglycolipids, gangliosides, sialic acid or brain phospholipids; inclusion of the sialoganglioside component in the liposome membrane was shown to decrease the uptake of liposome by liver tissue to permit increased amounts of encapsulated EDTA to reach other organs [M. M. Jonah et al, Biochimica et Biophysica Acta., 541, 321-333 (1978)].
Investigations have been made into the interaction of gangliosides and membrane-forming lipid materials. For example, a bilayer membrane structure can be formed by complementary packing of cone-shaped phosphatidylethanolamine material and inverted cone-shaped ganglioside GD.sub.1.sbsb.a material; these bilayer structures have been mentioned as useful in regulating membrane fluidity by changing ganglioside concentrations within the membrane in order to study Sendai virus induced leakage of the liposome [Y. Tsao et a, Biochem Biophys Acta, 900(1), 79-87 (1987)]. Artificial planar bilayer membranes have been made which are composed of phospholipids and monosialoganglioside (GM.sub.1) micelles containing the ionophore gramicidin D. Membrane conductance was found to increase after the addition of GM.sub.1 micelles at various ionophore/ganglioside ratios [F. Gimbale et al, Journal of Neuroscience Research, 12, 355-375 (1984)].
It is known that certain ganglioside materials can exhibit pharmacological activity in biological systems. For example, Italian Patent No. 1,046,051 mentions use of mono-, di-, tri- and tetra-sialogangliosides for treatment of disorders in the central and peripheral nervous systems such as paralysis of oculomotor nerves neuralagia of the trigeminus, paralysis of the facial nerve (Bell's paralysis), acute polyradiculoneuritis (Guillain-Barre syndrome), radiculitis, traumatic lesions of peripheral nerves, lesions of peripheral nerves due to toxic substances, alcoholic and diabetic polyneuritis, obstetric paralysis, paralysing sciatics, touching motorneurons, lateral amyotrophic sclerosis, muscular myelopathic atrophy, progressive bulbar paralysis, chronic myasthenia (Lambert Eaton syndrome), muscular dystrophy, changes in nervous synaptic transmission at CNS and PNS level, secondary consciousness troubles, cranial traumatism, cerebrum vascular disorders, thromboses and embolisms.
In a publication of R. W. Ledeen [J. Neurosci Res., 12, 147-159 (1984)], there is a study of the neuritogenic and neuronotrophic properties of gangliosides showing that neurite formation is promoted by exogenously administered gangliosides. Exogenous gangliosides have been found to alter the onset lag of NGF-induced neurite recruitment of PC12 cells in the presence of fetal calf serum [R Katoh-Semba et al, Soc. Neurosci. Abst., 10(1), 37 (1984)]. In a study of ganglioside influence on neuronal sprouting, rabbit anti-GM antibodies were found to block NGF-induced dorsal root ganglia sprouting of chicken embryo, which by inference may indicate promotion of neurite formation by gangliosides [M. Schwartz et al, Proc. Natl. Acad. Sci. USA, 79, 6080-6083 (1982)]. U.S. Pat. No. 4,593,091 describes inner ester ganglioside derivatives characterized in having a lactonic ring formed from a carboxyl group of an N-acetyl-neuraminic acid or N-glycolylneuraminic acid bonded to a hydroxy group of a carbohydrate comprising an N-acetylgalactosamine or N-acetylglycosamine moiety and glucose or galactose moiety, such ganglioside inner esters being more useful than the parent gangliosides in stimulating nerve regeneration and healing damaged nerve tissue. European Patent Application No. 183,572 describes mixtures of gangliosides (Svennerholm structure types GM.sub.1, GD.sub.1.sbsb.a, GD.sub.1.sbsb.b, GT.sub.i.sbsb.b) extracted from cattle cerebral cortex to have analgesic activity, particularly for treating peripheral neuropathy, trigeminus neuralgia and herpes Zoster. European Patent No. 195,169 describes administration of ganglioside GM.sub.1 or its inner ester to increase cerebral blood flow without increase in arterial blood pressure for treatment of ischemia-induced cerebral stroke. U.S. Pat. No. 4,639,437 describes treatment of peripheral and central nervous disorders due to nerve damage by injury or disease with systemic administration of inner ester ganglioside derivatives in nebulized liquid or powder form by inhalation through respiratory membranes